When chemotherapy is used to treat cancer cells measures are taken to limit side effects that otherwise might affect parts of the body not associated with the cancer. Examples of chemotherapeutic agents include the following: alkylating agents such as cisplatin, and carboplatin that chemically modify the cell's DNA which ultimately leads to apoptosis; anthracyclines such as doxorubicin that inhibit DNA and RNA synthesis and prevent replication of the rapidly-growing cancer cells; plant alkaloids such as paclitaxel and docetaxel that work by interfering with the normal microtubule formation during cell division.
The unwanted side effects may be short-term, long term, or permanent, even death. Chemotherapy can cause permanent damage to other organs such as the heart, liver, kidney, lungs, and reproductive organs. For example, cardiotoxicity is a common problem for anthracycline based treatment and is caused by many factors such as free radical formation in the heart or buildup of metabolic products of the anthracycline in the heart. Other side effects from chemotherapy include pain, diarrhea, constipation, mouth sores, hair loss, nausea and vomiting, as well as blood-related side effects.
Chemoprotective agents protect healthy tissue from the toxic effects of cancer drugs. For example, cardioprotective agents such as dexrazoxane can be used to reduce the effect of cardiotoxity. Another example is S-2-3-aminopropil amino ethyl phosphorotioic acid, commonly known as Amifostine™. It was approved by the Federal Drug Administration (FDA) in 1995. It helps to reduce the level of renal injury in cancer patients treated with chemotherapy through myelosuppression of alkylating agents.
Ultrasound mediated delivery of drugs, genetic materials, and other therapeutic agents are promising applications of ultrasound therapy. In these approaches, particles (nanoparticles, liposomes, microcapsules, microbubbles, etc.) incorporate therapeutic agents onto the surface, within the outer coating, within the core of the particle, or in proximity to the particles. Spatially localized treatments are achieved by site-targeted delivery with specific targeting ligands, but also through exposure of a volume of tissue to activating ultrasound energy. Targeting ligands enable binding to specific pathological epitopes and can be incorporated onto the particle surface through avidin-biotin linkages, chemical, or electrostatic interactions. Ultrasound is then introduced to enhance release of the drug. The mechanisms for ultrasound mediated delivery are dependent on the type of particle and ultrasound exposure but can be generally characterized as mechanical (pressure, radiation force, acoustic cavitation) or thermal effects.
Damage to other tissues and organs is an unwanted side effect of many treatment methods such as chemotherapy. All chemotherapeutic methods lead to depression of immune system through decrease in white blood cell, red blood cell, and platelet counts. Liposomal and site targeted formulations have decreased side effects, because delivery of the chemotherapy drug is localized to the site in the body to which ultrasound is applied. However, the side effects, although decreased, are not eliminated. Cardiotoxicity, one of the serious side effects, often presents as EKG changes and arrhythmias, or as a cardiomyopathy leading to congestive heart failure, sometimes presenting many years after treatment. Due to this, there is a maximum cumulative lifetime dose that a patient can be administered. Treatment is usually stopped upon reaching the maximum cumulative dose of the particular anthracycline. The chemotherapy treatment requires careful monitoring of cardiac function with radionuclide angiography. The patient is required to make several visits to the clinic or hospital for treatment.
While the chemoprotective agents can be used to reduce the side effects, the drug and chemoprotective agents cannot be administered simultaneously since they are intended to have opposite effects on the cells.
The cytotoxic effects of doxorubicin exist for several hours, which is helpful to achieve a sufficient level of cell death at the tumor site; however, this causes prolonged exposure to other critical organs as well.